This project represents an experimental model system for the study of human and animal disease caused by the African trypanosomes. A continuation of studies which examine the immunobiological relationship between host and parasite in Trypanosoma brucei rhodesiense infected inbred mice is proposed. The specific aims of the project are (1) to define at the molecule and cellular levels the nature of host immune responses to defined epitopes of trypanosome variant-specific and invariant antigens; (2) to examine at the molecular and cellar levels the means by which infected hosts regulate parasite-specific immune responses; (3) to determine how non-MHC-associated genetic differences influence the overall resistance status of the infected host strain; and (4) to define the molecular and genetic bases of virulence expression in trypanosomes which alter host immunity and resistance characteristics. Contemporary immunology and molecular biology form the conceptual and technique framework of this project.